The natural history and management of gastrinomas and other malignant pancreatic endocrine tumors (PETs) is largely based on antedotal reports and small series because of their relatively low incidence. Gastrinomas are the most common symptomatic, malignant PET and sufficient numbers of these patients (n=265) have been entered into our protocols to allow systematic assessment. Studies are now underway, evaluating the natural history of these tumors, definition of factors determining prognosis and improved methods to diagnose these tumors. The initial results of the assessment of prognostic factors was published this year (J. Clin. Oncol. 17, 615, 1999), demonstrating the importance of disease extent, location, development of bone, liver or lymph node metastases and/or Cushings syndrome as a prognostic factor. Detailed studies are also underway investigating the management of these tumors including assessment of newer methods to localize tumor extent (endoscopic ultrasound, somatostatin receptor scintigraphy [SRS]), definition of the role of surgical resection in both limited metastatic disease and patients with no hepatic metastases; the role of aggressive resection in selected patients, and the role of surgery in patients with MEN1 or without MEN1. The specificity of SRS, the most sensitive imaging modality was prospectively studied this year [J. Nucl. Med. 40, 539, 1999. It was demonstrated that false positive results can occur in 12% of patients and need to be considered. The possible side-effects of longterm acid secretory control are being examined including effects on vitamin B-12 and iron absorption as well as the development of gastric carcinoids. Lastly, medical treatment of advanced disease by chemotherapy, use of interferon, radiation and somatostatin analogues is being examined. This year the results of our long-term prospective study of surgery for cure in patients with ZES was reported (NEJM 341:635, 1999) involving 151 consecutive cases. This study established the value of surgery for cure in patients without MEN1, and demonstrates its ineffectiveness in patients without MEN-1. - Zollinger-Ellison syndrome, gastrinoma, islet cell tumor, carcinoid tumor, hypergastrinemia